US10617725B2 - Composition containing Bifidobacterium for alleviating, preventing or treating rheumatoid arthritis - Google Patents
Composition containing Bifidobacterium for alleviating, preventing or treating rheumatoid arthritis Download PDFInfo
- Publication number
- US10617725B2 US10617725B2 US15/977,466 US201815977466A US10617725B2 US 10617725 B2 US10617725 B2 US 10617725B2 US 201815977466 A US201815977466 A US 201815977466A US 10617725 B2 US10617725 B2 US 10617725B2
- Authority
- US
- United States
- Prior art keywords
- rheumatoid arthritis
- att
- bifidobacterium bifidum
- group
- alleviating
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 206010039073 rheumatoid arthritis Diseases 0.000 title claims abstract description 91
- 239000000203 mixture Substances 0.000 title claims abstract description 16
- 241000186000 Bifidobacterium Species 0.000 title abstract description 12
- 241000186016 Bifidobacterium bifidum Species 0.000 claims abstract description 44
- 229940002008 bifidobacterium bifidum Drugs 0.000 claims abstract description 44
- 238000000034 method Methods 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 235000013305 food Nutrition 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 6
- 239000003814 drug Substances 0.000 abstract description 13
- 239000006041 probiotic Substances 0.000 abstract description 3
- 230000000529 probiotic effect Effects 0.000 abstract description 3
- 235000018291 probiotics Nutrition 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 2
- 230000003389 potentiating effect Effects 0.000 abstract description 2
- 238000004458 analytical method Methods 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 230000000968 intestinal effect Effects 0.000 description 12
- 238000009826 distribution Methods 0.000 description 11
- 229940079593 drug Drugs 0.000 description 10
- 230000000813 microbial effect Effects 0.000 description 10
- 102000004890 Interleukin-8 Human genes 0.000 description 8
- 108090001007 Interleukin-8 Proteins 0.000 description 8
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 8
- 229940096397 interleukin-8 Drugs 0.000 description 8
- 229960000485 methotrexate Drugs 0.000 description 8
- 239000003435 antirheumatic agent Substances 0.000 description 7
- 230000002550 fecal effect Effects 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 238000012790 confirmation Methods 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 102000000503 Collagen Type II Human genes 0.000 description 5
- 108010041390 Collagen Type II Proteins 0.000 description 5
- 206010009944 Colon cancer Diseases 0.000 description 5
- 208000029742 colonic neoplasm Diseases 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 108020004465 16S ribosomal RNA Proteins 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 210000000936 intestine Anatomy 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- 201000008482 osteoarthritis Diseases 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 229960000074 biopharmaceutical Drugs 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 108040006858 interleukin-6 receptor activity proteins Proteins 0.000 description 3
- 210000003041 ligament Anatomy 0.000 description 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 3
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000003470 adrenal cortex hormone Substances 0.000 description 2
- 235000013334 alcoholic beverage Nutrition 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 238000007622 bioinformatic analysis Methods 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002988 disease modifying antirheumatic drug Substances 0.000 description 2
- -1 elixirs Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000007481 next generation sequencing Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 2
- 229960001940 sulfasalazine Drugs 0.000 description 2
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010051728 Bone erosion Diseases 0.000 description 1
- 244000206911 Candida holmii Species 0.000 description 1
- 235000002965 Candida holmii Nutrition 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010061619 Deformity Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 101001055222 Homo sapiens Interleukin-8 Proteins 0.000 description 1
- 241000202564 Kalopanax Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 229960002964 adalimumab Drugs 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 210000001188 articular cartilage Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 210000004922 colonic epithelial cell Anatomy 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000005786 degenerative changes Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 210000000281 joint capsule Anatomy 0.000 description 1
- 230000008407 joint function Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000015122 lemonade Nutrition 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 235000015096 spirit Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 210000001258 synovial membrane Anatomy 0.000 description 1
- 210000002437 synoviocyte Anatomy 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/745—Bifidobacteria
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/306—Foods, ingredients or supplements having a functional effect on health having an effect on bone mass, e.g. osteoporosis prevention
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/51—Bifidobacterium
- A23V2400/517—Bifidum
-
- A23Y2300/25—
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
Definitions
- the present invention relates to a composition containing Bifidobacterium for alleviating, preventing or treating rheumatoid arthritis.
- Degenerative arthritis is the most common inflammatory disease of the joints, which involves inflammation and pain, when bones and ligaments constituting the joints are damaged due to progressive damage or degenerative changes in the cartilage that protects the joints.
- Degenerative arthritis is classified into primary (idiopathic) arthritis which occurs by factors such as age, gender, genetic factors, obesity, specific joint sites and the like, without specific congenital factors, and secondary (subsequent) arthritis caused by trauma, disease, deformity and the like that may damage the articular cartilage.
- rheumatoid arthritis is a chronic inflammatory disease characterized by inflammation and proliferation of synovial cells.
- Rheumatoid arthritis induces osteoporosis, bone erosion and so on, unlike degenerative arthritis.
- Rheumatoid arthritis progresses in the following stages: inflammation of the synovial membrane spreads into the joint capsule, ligament and tendon (stage 1); the gap between the joints becomes narrow and the tension between the joint membrane and ligament disappears due to gradual destruction of the joint cartilage (stage 2); inflammation penetrates into the bones, causing partial erosion of the bones (stage 3); and the joint function is lost (stage 4).
- non-steroidal anti-inflammatory drugs such as NSAIDs, salicylates and COX-2 inhibitors; adrenal cortical hormone drugs such as prednisolone and triamcinolone; disease-modifying antirheumatic drugs (DMARDs) such as methotrexate and sulfasalazine; and biologics such as etanercept, infliximab and adalimumab have been conventionally used.
- NSAIDs/NAIDs non-steroidal anti-inflammatory drugs
- DMARDs disease-modifying antirheumatic drugs
- biologics such as etanercept, infliximab and adalimumab have been conventionally used.
- non-steroidal anti-inflammatory drugs and adrenocortical hormone preparations are used in the early stage of symptom onset, and antirheumatic drugs are used in consideration of symptoms and disease activity.
- antirheumatic drugs are used in consideration of symptoms and disease activity.
- biologics or combination therapies are used in clinical practice.
- nonsteroidal anti-inflammatory drugs such as NSAIDs, which entail relatively low treatment costs, cause gastrointestinal side effects, and antirheumatic drugs such as methotrexate and sulfasalazine also cause gastrointestinal disorders.
- Patent Document 1 Korean Patent Laid-open No. 10-2011-0035100 (Apr. 6, 2011) discloses a method for producing a herbal composition for treating osteoarthritis containing a Kalopanax bark extract biotransformed by Saccharomyces cerevisiae mutant BH02 or Saccharomyces exiguus mutant BH12.
- the present invention has been made in view of the above problems, and it is an object of the present invention to isolate a novel microorganism effective for alleviating, preventing or treating rheumatoid arthritis and provide a method of using the microorganism.
- Bifidobacterium bifidum ATT accession number: KCTC13474BP
- KCTC13474BP accession number: KCTC13474BP
- a food composition for alleviating rheumatoid arthritis comprising a culture solution of Bifidobacterium bifidum ATT (accession number: KCTC13474BP), or a dried powder thereof.
- a pharmaceutical composition for preventing or treating rheumatoid arthritis comprising a culture solution of Bifidobacterium bifidum ATT (accession number: KCTC13474BP), or a dried powder thereof.
- FIG. 1 shows an analysis result of intestinal microbial flora distributions on normal subjects and Korean rheumatoid arthritis patients (Normal: normal subject, RA: rheumatoid arthritis patient);
- FIG. 2 shows an analysis result of intestinal microbial flora distributions depending on stage and treatment method on normal subjects and Korean rheumatoid arthritis patients (Normal: normal group, Preclinical: group with no rheumatoid arthritis symptom, Drug Naive: group diagnosed with rheumatoid arthritis, DMARD: group treated with an antirheumatic drug (methotrexate (MTX)), BL: group treated with a primary biologic (TNF inhibitor), BS: group treated with a secondary biologic (IL-6R mAb, CTLA4-Ig));
- MTX antirheumatic drug
- BL group treated with a primary biologic
- BS group treated with a secondary biologic
- IL-6R mAb IL-6R mAb, CTLA4-Ig
- FIG. 3 shows an analysis result of adhesion to the intestine of the Bifidobacterium bifidum ATT found by the present invention
- FIG. 4 shows an analysis result of a control effect of Bifidobacterium bifidum ATT on rheumatoid arthritis [(A) comparison in rheumatoid arthritis score (p ⁇ 0.001***, p ⁇ 0.01**, p ⁇ 0.05*), (B) comparison in rheumatoid arthritis incidence (p ⁇ 0.001***, p ⁇ 0.01**, p ⁇ 0.05*)];
- FIG. 5 shows an analysis result of inhibition on IL-8 secretion of Bifidobacterium bifidum ATT in human colon cancer cell line HT-29 [(A) IL-1 ⁇ treatment group, (B) TNF ⁇ treatment group, (C) LPS treatment group]; and
- FIG. 6 shows an analysis result of IgG antibody expression in the rheumatoid arthritis-induced mouse serum [(A): IgG, (B): IgG2a, (C): IgG specific to rheumatoid arthritis antibody (type ii collagen; Cii) (Cii-specific lgG), (D): IgG2a specific to rheumatoid arthritis antibody (type ii collagen; Cii) (Cii-specific IgG2a); Vehicle: group to which Bifidobacterium bifidum ATT is not administered, Bifidobacterium biffidum ATT: group to which Bifidobacterium bifidum ATT is administered; p ⁇ 0.05*).
- the present invention provides Bifidobacterium bifidum ATT (accession number: KCTC13474BP) effective for preventing or treating rheumatoid arthritis.
- Bifidobacterium bifidum ATT accession number: KCTC13474BP
- the present invention proved that Bifidobacterium bifidum ATT is capable of being highly adhered to intestinal cells, slowing down the onset of rheumatoid arthritis and significantly reducing the incidence of rheumatoid arthritis.
- the present invention provides a food composition for alleviating rheumatoid arthritis which contains a culture solution of Bifidobacterium bifidum ATT (accession number: KCTC13474BP) or a dried powder thereof.
- Bifidobacterium bifidum ATT accession number: KCTC13474BP
- the Bifidobacterium bifidum ATT is preferably present in an amount of 0.00001 to 50% by weight with respect to the weight of the food composition for alleviating rheumatoid arthritis.
- Bifidobacterium bifidum ATT When the Bifidobacterium bifidum ATT is present in an amount of less than 0.00001% by weight, effects thereof are unsatisfactory, and when the Bifidobacterium bifidum ATT is present in an amount higher than 50% by weight, the effects thereof are poor, compared to the amount of Bifidobacterium bifidum ATT used, thus making it less economical.
- the food composition for alleviating rheumatoid arthritis is selected from the group consisting of meat, cereal, caffeinated beverages, regular beverages, chocolate, bread, snacks, confectionery, candy, pizza, jelly, noodles, gums, dairy products, ice cream, alcoholic beverages, alcoholic drinks, vitamin complexes and other health supplement foods, but the present invention is not limited thereto.
- the present invention provides a pharmaceutical composition for preventing or treating rheumatoid arthritis which contains a culture solution of Bifidobacterium bifidum ATT (accession number: KCTC13474BP) or a dried powder thereof.
- the pharmaceutical composition for preventing or treating rheumatoid arthritis may further include a pharmaceutically acceptable carrier, diluent or excipient, in addition to the active ingredient.
- suitable carriers, excipients or diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, amorphous cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and a combination thereof.
- the drug which is the pharmaceutical composition for preventing or treating rheumatoid arthritis according to the present invention, may further include one or more selected from fillers, anti-coagulants, lubricants, wetting agents, perfumes, emulsifiers and preservatives.
- the pharmaceutical composition for preventing or treating rheumatoid arthritis according to the present invention is preferably formulated depending on application method.
- the pharmaceutical composition is preferably formulated by selecting a method well-known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to mammals.
- examples of the formulation may include any one selected from plasters, granules, lotions, liniments, lemonades, aromatic waters, powders, syrups, ophthalmic ointments, liquids and solutions, aerosols, extracts, elixirs, ointments, fluidextracts, emulsions, suspensions, decoctions, infusions, ophthalmic solutions, tablets, suppositories, injections, spirits, cataplasma, capsules, creams, troches, tinctures, pastes, pills, and soft or hard gelatin capsules.
- the dose of the pharmaceutical composition for preventing or treating rheumatoid arthritis according to the present invention is preferably determined in consideration of method of administration, age, gender and weight of patients and severity of diseases.
- the pharmaceutical composition for preventing or treating rheumatoid arthritis according to the present invention can be administered at least once in a daily dose of 0.00001 to 100 mg/kg (body weight).
- the dose is provided as an example and can be changed by the physician's prescription depending on the conditions of a patient.
- fecal samples were collected from 3 normal subjects and 79 Korean rheumatoid arthritis patients, and stored at ⁇ 80° C. Then, in order to conduct next generation sequencing on the fecal samples, bacterial genomic DNAs were isolated from the fecal samples and 16S rRNA genes specific to microorganisms were amplified to produce a library. The 16S rRNA genes of the library were decoded using Misep available from Illumina Inc. The decoded sequences were subjected to bio-informatic analysis using QllME1.9.1 (open-source bioinformatic pipeline) ( FIG. 1 ). FIG.
- the group with no rheumatoid arthritis symptom means a group of patients who show an increase in RA (rheumatoid arthritis) index, but have no rheumatoid arthritis symptoms, and the group diagnosed with rheumatoid arthritis (Drug Naive Rheumatoid Arthritis) means a group of patients who are diagnosed with rheumatoid arthritis, but do not take any drug.
- fecal samples were collected from the subjects' fecal samples and stored at ⁇ 80° C. Then, in order to conduct next generation sequencing on the fecal samples, bacterial genomic DNAs were isolated from the fecal samples and 16S rRNA genes specific to microorganisms were amplified to produce a library.
- the 16S rRNA genes of the library were decoded using Misep available from Illumina Inc. The decoded sequences were subjected to bio-informatic analysis using QllME1.9.1 (open-source bioinformatic pipeline) ( FIG. 2 ).
- FIG. 1 open-source bioinformatic pipeline
- Normal a normal group
- Preclinical a group with no rheumatoid arthritis symptom
- Drug Naive a group diagnosed with rheumatoid arthritis
- DMARD a group treated with an antirheumatic drug (methotrexate (MTX)
- BL a group treated with a primary biologic (TNF inhibitor)
- BS a group treated with a secondary biologic (IL-6R mAb, CTLA4-Ig)).
- the patient group to which a biologic is secondarily (or tertiary) administered, does not react to the primary biologic and thus shows the lowest Bifidobacterium distribution among all the groups, and shows a significant decrease in Bifidobacterium distribution as compared to the normal subject (p ⁇ 0.01).
- the present inventors chose a variety of Bifidobacterium genera from human feces, chose Bifidobacterium bifidum ATT effective for treating rheumatoid arthritis through preliminary tests, deposited at the Korea Research Institute of Bioscience and Biotechnology on Jan. 30, 2018, and then received an accession number of KCTC13474BP.
- Test Example 1 Confirmation of Adhesion to Intestine of Bifidobacterium bifidum ATT
- the human colonic epithelial cell line, Caco-2 was seeded at a concentration of 1 ⁇ 10 5 cells/well on a 24-well plate and cultured for 14 days. Then, the cells were treated with 1 ⁇ 10 8 CFU of Bifidobacterium bifidum ATT having been cultured in MRS liquid medium for 18 hours and then cultured for 1 hour. After culturing for one hour, a beneficial bacteria suspension was injected into the cells, the cells were washed with PBS three times to remove the remaining cells and were harvested with trypsin EDTA, and the genomic DNAs were extracted.
- FIG. 3 shows an analysis result of adhesion to the intestine of the Bifidobacterium bifidum ATT found by the present invention.
- the adhesion of bacteria is strong when the number of bacteria adhered to 100 Caco-2 cells is more than 40.
- the Bifidobacterium bifidum ATT exhibits considerably excellent adhesion to intestinal cells.
- Bifidobacterium bifidum ATT inhibits secretion of IL-8 in the human colon cancer cell line
- Bifidobacterium bifidum ATT was orally administered at a concentration of 100 mg/kg to rheumatoid arthritis subjects daily for one week after the onset of rheumatoid arthritis.
- Rheumatoid arthritis started to develop 21 days after disease induction, and the group, to which Bifidobacterium bifidum ATT was administered, started to develop the disease 30 days after disease induction, but showed significant inhibition of the disease, compared to the rheumatoid arthritis control group.
- FIG. 4 shows an analysis result of a control effect of Bifidobacterium bifidum ATT on rheumatoid arthritis [(A) comparison in rheumatoid arthritis score (p ⁇ 0.001***, p ⁇ 0.01**, p ⁇ 0.05*), (B) comparison in rheumatoid arthritis incidence (p ⁇ 0.001***, p ⁇ 0.01**, p ⁇ 0.05*)].
- IL-8 interleukin 8
- IL-1 ⁇ , TNF- ⁇ and LPS as stimulus sources
- Bifidobacterium bifidum ATT (1 ⁇ 10 8 CFU/ml) were applied to the HT-29 cell monolayer and cultured for 6 hours.
- IL-8 secreted from the cells the supernatant was collected and analyzed using a Human IL-8 ELISA Set (BD, San Diego, USA) ( FIG. 5 ).
- FIG. 5 Human IL-8 ELISA Set
- FIG. 5 shows an analysis result of inhibition on IL-8 secretion of Bifidobacterium bifidum ATT in human colon cancer cell line HT-29 [(A) IL-1 ⁇ treatment group, (B) TNF ⁇ treatment group, (C) LPS treatment group].
- Bifidobacterium bifidum ATT was treated in combination with three stimulus sources (IL-1 ⁇ , TNF- ⁇ , LPS)
- IL-8 expression caused by the stimulus sources was similar to that of the non-treatment group and was significantly decreased, compared to the group treated with one kind of stimulus source (p ⁇ 0.05).
- Test Example 4 Analysis of IgG Antibody Expression in Rheumatoid Arthritis Animal Serum
- mice In order to analyze expression of IgG antibody in the mouse serum, mouse subjects of Bifidobacterium bifidum ATT non-treatment (Vehicle) and treatment groups ( Bifidobacterium bifidum ATT) 63 days after induction of rheumatoid arthritis were subjected to orbital blood collection and the serum was isolated from the blood.
- IgG, IgG2a, IgG specific to the rheumatoid arthritis antibody type ii collagen; Cii) (Cii-specific lgG), and IgG2a specific to the rheumatoid arthritis antibody (Cii-specific IgG2a) were measured from the isolated serum ( FIG. 6 ).
- FIG. 6 In order to analyze expression of IgG antibody in the mouse serum, mouse subjects of Bifidobacterium bifidum ATT non-treatment (Vehicle) and treatment groups ( Bifidobacterium bifidum
- FIG. 6 shows an analysis result of IgG antibody expression in the rheumatoid arthritis-induced mouse serum [(A): IgG, (B): IgG2a, (C): IgG specific to the rheumatoid arthritis antibody (type ii collagen; Cii) (Cii-specific lgG), (D): IgG2a specific to the rheumatoid arthritis antibody (type ii collagen; Cii) (Cii-specific IgG2a); Vehicle: group to which Bifidobacterium bifidum ATT is not administered, Bifidobacterium bifidum ATT: group to which Bifidobacterium bifidum ATT is administered; p ⁇ 0.05*].
- the Bifidobacterium bifidum ATT newly isolated according to the present invention is useful as a rheumatoid arthritis medicine or a probiotic material for alleviating rheumatoid arthritis owing to potent efficacy in treating rheumatoid arthritis.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Mycology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Nutrition Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Molecular Biology (AREA)
- Physical Education & Sports Medicine (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Physiology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (3)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020180012354A KR102023700B1 (en) | 2018-01-31 | 2018-01-31 | Composition for prevention or treatment of rheumatoid arthritis with Bifidobacterium |
KR10-2018-0012354 | 2018-01-31 |
Publications (2)
Publication Number | Publication Date |
---|---|
US20190231830A1 US20190231830A1 (en) | 2019-08-01 |
US10617725B2 true US10617725B2 (en) | 2020-04-14 |
Family
ID=67393047
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US15/977,466 Active US10617725B2 (en) | 2018-01-31 | 2018-05-11 | Composition containing Bifidobacterium for alleviating, preventing or treating rheumatoid arthritis |
Country Status (2)
Country | Link |
---|---|
US (1) | US10617725B2 (en) |
KR (1) | KR102023700B1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20220211775A1 (en) * | 2020-03-19 | 2022-07-07 | Bifido Co., Ltd. | Food composition and pharmaceutical composition for inhibiting sjogren's syndrome each containing bifidobacterium pseudocatenulatum c-rapo (kctc13986bp) and bifidobacterium bifidum att (kctc13474bp) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102263884B1 (en) * | 2019-10-11 | 2021-06-14 | 가톨릭대학교 산학협력단 | Bifidobacterium pseudocatenulatum C-RAPO for improvement, prevention or treatment of rheumatoid arthritis and composition comprising the same |
KR102343938B1 (en) * | 2020-09-02 | 2021-12-28 | 주식회사 비피도 | Composition for improving inflammation containing recombinant Bifidobacterium bifidum BGN4 |
CN116286439A (en) * | 2022-07-13 | 2023-06-23 | 四川大学 | Bifidobacterium bifidum from infant intestinal tracts and application thereof |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20110035100A (en) | 2009-09-29 | 2011-04-06 | (주)비에이치생명과학 | Herbal medicine for treating arthrits and herbal composition containing it |
US20140056852A1 (en) * | 2011-01-31 | 2014-02-27 | Naturwohl Pharma Gmbh | Bifidobacterium bifidum strains for application in gastrointestinal diseases |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5031249B2 (en) | 2006-03-22 | 2012-09-19 | 学校法人北里研究所 | Bacteria-containing composition having anti-inflammatory effect |
CN102115721B (en) | 2008-05-08 | 2012-09-26 | 景岳生物科技股份有限公司 | Lactobacillus isolated strains with anti-inflammatory activity and use thereof |
CN104546945A (en) * | 2014-09-30 | 2015-04-29 | 深圳华大基因科技有限公司 | Application of bifidobacterium bifidum in treating or preventing rheumatoid arthritis or related diseases thereof |
-
2018
- 2018-01-31 KR KR1020180012354A patent/KR102023700B1/en active IP Right Grant
- 2018-05-11 US US15/977,466 patent/US10617725B2/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20110035100A (en) | 2009-09-29 | 2011-04-06 | (주)비에이치생명과학 | Herbal medicine for treating arthrits and herbal composition containing it |
US20140056852A1 (en) * | 2011-01-31 | 2014-02-27 | Naturwohl Pharma Gmbh | Bifidobacterium bifidum strains for application in gastrointestinal diseases |
Non-Patent Citations (7)
Title |
---|
Coore et al. "Production of Concentrated Bifidobacterium bifidum" J. Chem. Tech. Biotechnol 1992, 53, pg. 189-194 (Year: 1992). * |
Dinakar et al. "Growth and Viability of Bifidobacterium bifidum in Cheddar Cheese" J Dairy Sci 77:2854-2864, 1994 (Year: 1994). * |
Feng et al., English Translation of CN104546945 publised in Chinese on Apr. 29, 2015, 57 pgs (Year: 2015). * |
Riedel et al. "Interaction of bifidobacteria with Caco-2 cells-adhesion and impact on expression profiles" International Journal of Food Microbiology 110 (2006) 62-68 (Year: 2006). * |
Riedel et al. "Interaction of bifidobacteria with Caco-2 cells—adhesion and impact on expression profiles" International Journal of Food Microbiology 110 (2006) 62-68 (Year: 2006). * |
Vinderola et al. "Culture media for the enumeration of Bifidobacterium bifidum and Lactobacillus acidophilus in the presence of yoghurt bacteria" International Dairy Journal 9 (1999) 497}505 (Year: 1999). * |
Zamani et al. "Clinical and metabolic response to probiotic supplementation in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled trial" International Journal of Rheumatic Diseases 2016; 19: 869-879 (Year: 2016). * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20220211775A1 (en) * | 2020-03-19 | 2022-07-07 | Bifido Co., Ltd. | Food composition and pharmaceutical composition for inhibiting sjogren's syndrome each containing bifidobacterium pseudocatenulatum c-rapo (kctc13986bp) and bifidobacterium bifidum att (kctc13474bp) |
US11701395B2 (en) * | 2020-03-19 | 2023-07-18 | Bifido Co., Ltd. | Food composition and pharmaceutical composition for inhibiting Sjogren's syndrome each containing Bifidobacterium pseudocatenulatum C-RAPO (KCTC13986BP) and Bifidobacterium bifidum ATT (KCTC13474BP) |
Also Published As
Publication number | Publication date |
---|---|
KR20190099360A (en) | 2019-08-27 |
US20190231830A1 (en) | 2019-08-01 |
KR102023700B1 (en) | 2019-09-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10617725B2 (en) | Composition containing Bifidobacterium for alleviating, preventing or treating rheumatoid arthritis | |
JP6839298B2 (en) | New lactic acid bacteria and their uses | |
Willich et al. | Rose hip herbal remedy in patients with rheumatoid arthritis–a randomised controlled trial | |
CN114410548B (en) | Novel lactobacillus having various functions and use thereof | |
AU2018341734B2 (en) | Composition for diagnosis and treatment of alcoholic liver disease, using change in short-chain fatty acid producing gut bacterial community | |
JP5031249B2 (en) | Bacteria-containing composition having anti-inflammatory effect | |
KR100913405B1 (en) | Compositions for preventing or treating th2-mediated immune diseases | |
US9737577B2 (en) | Lactic acid bacterium-containing preparation | |
KR20080091743A (en) | Pharmaceutical and food compositions for preventing or treating arthritis comprising lactic acid bacteria and collagen as active ingredients | |
CN111315386A (en) | Biotransformation of Oleuropein | |
MX2012009945A (en) | Lactic acid bacterium-containing preparation. | |
CN112105371A (en) | Lipopolysaccharide-controlling intestinal bacteria and uses thereof | |
CN111902531B (en) | Bifidobacterium longum RAPO strain for improving, preventing or treating rheumatoid arthritis and composition comprising the same | |
JP2021519763A (en) | Compositions and Methods for Treating Inflammatory Bowel Disease | |
KR20120112510A (en) | Dna damage repair promoter for oral application, and elastase activity inhibitor for oral application | |
KR20210141541A (en) | Bacteria of the family Christensenellae for the prevention and/or treatment of chronic inflammatory diseases and/or inflammatory gastrointestinal diseases and/or cancer | |
KR20230124601A (en) | Bacterial compositions designed to treat graft-versus-host disease | |
KR100913406B1 (en) | Compositions for preventing or treating th1-mediated immune diseases | |
CN104546930B (en) | Haemophilus parainfluenzae is treating or preventing the application in rheumatoid arthritis or its related disease | |
CN104546938B (en) | Extremely huge Megamonas is treating or preventing the application in rheumatoid arthritis | |
US11484557B2 (en) | Human-derived Lactobacillus fermentum MG4231 or Lactobacillus fermentum MG4244 strain having anti-obesity activity, and composition comprising same | |
CN104546947B (en) | Lactobacillus crispatus is treating or preventing the application in rheumatoid arthritis | |
Maixent et al. | Clinical effects of Lactobacillus strains as probiotics in the treatment of irritable bowel syndrome. Results from the LAPIBSS trial: Future objectives | |
CA3099880A1 (en) | Compositions comprising bacterial strains | |
Bhattacharya | Probiotics and herbals as a boom in treatment of ulcerative colitis |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: BIFIDO CO., LTD., KOREA, REPUBLIC OF Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:JI, GEUN EOG;JEONG, YUNJU;FANG, HUI;AND OTHERS;REEL/FRAME:045781/0162 Effective date: 20180509 Owner name: THE CATHOLIC UNIVERSITY OF KOREA INDUSTRY-ACADEMIC Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:JI, GEUN EOG;JEONG, YUNJU;FANG, HUI;AND OTHERS;REEL/FRAME:045781/0162 Effective date: 20180509 Owner name: THE CATHOLIC UNIVERSITY OF KOREA INDUSTRY-ACADEMIC COOPERATION FOUNDATION, KOREA, REPUBLIC OF Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:JI, GEUN EOG;JEONG, YUNJU;FANG, HUI;AND OTHERS;REEL/FRAME:045781/0162 Effective date: 20180509 |
|
FEPP | Fee payment procedure |
Free format text: ENTITY STATUS SET TO UNDISCOUNTED (ORIGINAL EVENT CODE: BIG.); ENTITY STATUS OF PATENT OWNER: SMALL ENTITY |
|
FEPP | Fee payment procedure |
Free format text: ENTITY STATUS SET TO SMALL (ORIGINAL EVENT CODE: SMAL); ENTITY STATUS OF PATENT OWNER: SMALL ENTITY |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: FINAL REJECTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NOTICE OF ALLOWANCE MAILED -- APPLICATION RECEIVED IN OFFICE OF PUBLICATIONS |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: AWAITING TC RESP, ISSUE FEE PAYMENT VERIFIED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: PUBLICATIONS -- ISSUE FEE PAYMENT VERIFIED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NOTICE OF ALLOWANCE MAILED -- APPLICATION RECEIVED IN OFFICE OF PUBLICATIONS |
|
STCF | Information on status: patent grant |
Free format text: PATENTED CASE |
|
AS | Assignment |
Owner name: BIFIDO CO., LTD., KOREA, REPUBLIC OF Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:THE CATHOLIC UNIVERSITY OF KOREA INDUSTRY-ACADEMIC COOPERATION FOUNDATION;REEL/FRAME:058773/0691 Effective date: 20220125 |
|
MAFP | Maintenance fee payment |
Free format text: PAYMENT OF MAINTENANCE FEE, 4TH YR, SMALL ENTITY (ORIGINAL EVENT CODE: M2551); ENTITY STATUS OF PATENT OWNER: SMALL ENTITY Year of fee payment: 4 |